Association of HLA-DRB1 and TNF genotypes with dengue hemorrhagic fever

Genes coding for human leukocyte antigen (HLA) class II molecules and tumor necrosis factor (TNF)-α are polymorphic and have been shown to influence susceptibility to infectious diseases. In the present study, HLA-DRB1, -DQB1 and TNF gene polymorphisms were investigated in 114 dengue patients (DEN) [85 dengue fever (DF) cases and 29 dengue hemorrhagic fever (DHF) cases] and 110 healthy controls (HCs) using PCR based methods. The frequencies of HLA-DRB1∗07 allele [DF vs. DHF, P = 0.0034, Pc = 0.044, OR 3.79] and HLA-DRB1∗07/∗15 genotype [DF vs. DHF, P = 0.00071, Pc = 0.038, OR 10.41] were significantly higher in DHF cases as compared to HCs and DF cases. Higher frequency of rs1800629 ‘G/A’ genotype was observed in DHF cases as compared to DF cases. The frequency of rs1799964 ‘C/C’ genotype of the TNF gene was found to be significantly higher in all patient groups compared to HCs [HCs vs. DEN, P = 0.0054, Pc = 0.0162, OR 3.57; HCs vs. DF, P = 0.036, OR 2.89; HCs vs. DHF, P = 0.0088, Pc = 0.0240, OR 5.11]. Presence of combination of HLA-DRB1∗07/∗15 with either rs1799964 ‘C/C’ genotype or rs1800629 ‘G/A’ genotype or both was present in 17.2% of DHF cases and 1.2% in HCs while this combination was not observed in DF cases. The results suggest that HLA-DRB1∗07/∗15 genotype in combination with TNF polymorphisms influence progression to DHF.

► Human leukocyte antigen (HLA) and TNF gene polymorphisms influence dengue disease severity.
► HLA class II and TNF gene polymorphisms studied in dengue cases (DF and DHF) and healthy controls.
► Higher frequencies of HLA-DRB1∗07/∗15 and rs1799964 C/C genotypes were observed in DHF.
► HLA-DRB1∗07/∗15 genotype in combination with TNF genotypes increases the risk of DHF.